We have enrolled over 50 participants in Protocol 07-EI-0145, "Ocular impact of X chromosome karyotype and sex hormones in Turner Syndrome and Premature Ovarian Failure." Premature ovarian failure (POF) is known to be associated with an increased risk of ocular surface disease (dry eye), likely due to the reduction of both estrogens and androgens seen in this condition. From preliminary data, we suspect that women with Turners syndrome (TS), (45, XO) a genetic abnormality that affects sex hormone levels, are also at increased risk of ocular surface disease. Comparing POF and TS women may allow us to distinguish different mechanisms for ocular surface disease, due to the different etiologies of hormonal (estrogen and androgen) alterations posed by POF and TS. In collaboration with NIDCR, we continued investigation of the natural history and treatment of the autoimmune exocrinopathy, Sjogren's Syndrome, associated with a particularly severe form of dry eye in which the pathogenesis involves dysregulated immune regulation. Specifically, protocol 06-D-0181, A randomized placebo controlled, proof of concept study of Raptiva, a humanized anti-CD11a monoclonal antibody in patients with Sjogren's syndrome, has been completed and the results are being analyzed. Several scientific abstracts are in preparation and Dry eye affects 5-30% of the population over the age of 50 years and risk factors include female sex, age, sex hormone alterations, refractive surgery, particular medications and infections and a variety of specific clinical diseases such as graft vs. host disease. Vision targeted health-related quality of life (QOL) instruments quantify an aspect of dry eye that is not measured in other ways. A wide variety of validated instruments that measure QOL and symptoms are available;however, clinically meaningful changes remain to be defined. We are well underway in enrolling participants in a clinical protocol to evaluate the comparability of QOL instruments in dry eye and control subjects administered via the web or conventional completion with paper and pen, the results from which will inform subsequent planned NEI FDA collaborative studies. Data analysis of the ocular response from a placebo-controlled, randomized controlled trial of systemic testosterone treatment in women with premature ovarian insufficiency is nearly completed. As part of our interest in outcome measures for ocular surface disease, data analysis is nearly complete from a one of its kind study on validation of digital imaging of ocular surface vital dye staining as an outcome measure for clinical trials.